Biophysical factors such as anisotropic topography composed of micro/nanosized structures are important for directing the fate of human bone marrow‐derived mesenchymal stem cells (hBM‐MSCs) and have been applied to neuronal differentiation. Via high‐throughput screening (HTS) methods based on topography gradients, the optimum topography is determined and translated toward a hierarchical architecture designed to mimic the nerve nano/microstructure. The polydimethylsiloxane (PDMS)‐based topography gradient with amplitudes (A) from 541 to 3073 nm and wavelengths (W) between 4 and 30 µm is developed and the fate commitment of MSC toward neuron lineage is investigated. The hierarchical structures, combining nano‐ and microtopography (W0.3/W26 parallel/perpendicular) are fabricated to explore the combined topography effects on neuron differentiation. From the immunofluorescent staining results (Tuj1 and MAP2), the substrate characterized by W: 26 µm; A: 2.9 µm shows highest potential for promoting neurogenesis. Furthermore, the hierarchical features (W0.3/W26 parallel) significantly enhance neural differentiation. The hBM‐MSCs on the hierarchical substrates exhibit a significantly lower percentage of nuclear Yes‐associated protein (YAP)/TAZ and weaker cell contractility indicating that the promoted neurogenesis is mediated by the cell tension and YAP/TAZ pathway. This research provides new insight into designing biomaterials for applications in neural tissue engineering and contributes to the understanding of topography‐mediated neuronal differentiation.
High-throughput screening (HTS) methods based on anisotropically topography gradients have been broadly used to investigate the interactions between cells and biomaterials. However, few studies focus on the optimum parameters of topography for osteogenic differentiation because the structures of topography are complex with multiple combinations of parameters. In this study, we developed polydimethylsiloxane (PDMS)-based wrinkled topography gradients (amplitudes between 144 and 2854 nm and wavelengths between 0.91 and 13.62 μm) and decoupled the wavelength and amplitude via imprinting lithography and shielded plasma oxidation. The PDMS wrinkle gradient was then integrated with the bottomless 96-well plate to constitute the wrinkled HTS platform, which consists of 70 different wrinkle parameters. From the in vitro culture of bone marrow stem cells, it was observed that aligned topography has an important influence on the macroscopic cell behavior (i.e., cell area, elongation, and nucleus area). Furthermore, the optimum wrinkle parameter (wavelength: 1.91 μm; amplitude: 360 nm) for osteogenic differentiation of stem cells was determined via this screening plate approach. This screening platform is not only beneficial for a better understanding of the interactions between topography and biomaterials but also advances the development of bone tissue engineering developments.
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